Pediatric Hematology/Oncology and ImmunopathologyPediatric Hematology/Oncology and ImmunopathologyВопросы гематологии/онкологии и иммунопатологии в педиатрии1726-17082414-9314Fund Doctors, Innovations, Science for Children113010.24287/j.1130PSUZOALITERATURE REVIEWОБЗОР ЛИТЕРАТУРЫReview Articleв текстеNormalized hemostasis as a new goal in the treatment of hemophilia A in children: the role of efanesoctocog alfaНормализованный гемостаз как новая цель лечения гемофилии А у детей: роль эфанесоктокога альфаhttps://orcid.org/0000-0003-4384-6754ZharkovPavel A.ЖарковПавел Александрович
Russian Federation

Dr. Med. Sci., Professor, a pediatrician, a hematologist, Head of the Department of Non-Malignant Hematology

д-р мед. наук, профессор, врач-педиатр, врач-гематолог, заведующий отделом незлокачественной гематологии

pavel.zharkov@fccho-moscow.ruThe Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology of Ministry of Healthcare of the Russian FederationФГБУ «Национальный медицинский исследовательский центр детской гематологии, онкологии и иммунологии им. Дмитрия Рогачева» Минздрава России300620262521911980805202612052026Copyright ©; 2026, «D. Rogachev NMRCPHOI»Copyright ©; 2026, ФГБУ «НМИЦ ДГОИ им. Дмитрия Рогачева» Минздрава России2026«D. Rogachev NMRCPHOI»ФГБУ «НМИЦ ДГОИ им. Дмитрия Рогачева» Минздрава Россииhttps://creativecommons.org/licenses/by/4.0https://hemoncim.com/jour/article/view/1130

Hemophilia A remains one of the major challenges in pediatric hematology, because it is during childhood that long-term disease outcomes develop, including the degree of joint damage, the level of physical activity, social adaptation, and quality of life in adulthood. Over the past decades, hemophilia A management has undergone a remarkable transformation, from treating individual bleeding episodes to early prophylaxis, with the aim of preserving joint health and achieving the so-called normalized hemostasis. This review summarizes current knowledge on hemophilic arthropathy, the evolution of the goals of prophylaxis, and the clinical and pharmacokinetic characteristics of efanesoctocog alfa, an ultra-long-acting factor VIII that functions independently of endogenous von Willebrand factor. Special attention is given to pivotal results from the phase III XTEND-Kids and XTEND-1 studies, indirect comparative analyses of standard and extended-half-life products, and non-factor therapy with emicizumab.

Гемофилия А остается одной из ключевых проблем современной педиатрической гематологии, поскольку именно в детском возрасте формируются долгосрочные исходы заболевания – степень поражения суставов, уровень физической активности, социальная адаптация и качество жизни во взрослом возрасте. За последние десятилетия подходы к терапии гемофилии А претерпели принципиальную трансформацию: от эпизодического лечения кровотечений к ранней профилактике, а затем к стратегической задаче сохранения полностью здоровых суставов и достижения так называемого нормализованного гемостаза. В обзоре представлены современные данные о патофизиологии гемофилической артропатии, эволюции целей профилактической терапии, а также клинические и фармакокинетические характеристики эфанесоктокога альфа – ультрапролонгированного препарата фактора VIII, функционально отделенного от эндогенного фактора фон Виллебранда. Особое внимание уделено результатам опорных исследований III фазы XTEND-Kids и XTEND-1, непрямым сравнительным анализам препаратов стандартного и пролонгированного периода полувыведения, а также нефакторной терапии эмицизумабом.

hemophilia Achildrenefanesoctocog alfanormalized hemostasisprophylaxishemophilic arthropathyfactor VIIIгемофилия Адетиэфанесоктоког альфанормализованный гемостазпрофилактикагемофилическая артропатияфактор VIIIЛившиц М.И., Попов В.Е., Колтунов И.Е., Свирин П.В., Левов А.В., Миронов И.Б. и др. Внутричерепные кровоизлияния у детей с гемофилией. Российский журнал детской гематологии и онкологии 2015;2(1):49–53. DOI: 10.17650/2311-1267-2015-1-49-53. [Livshitz M.I., Popov V.E., Koltunov I.E., Svirin P.V., Levov A.V., Mironov I.B. et al. Intracranial haemorrhage in a children suffering from heamofilia. Russian Journal of Pediatric Hematology and Oncology. 2015;2(1):49–53. (In Russ.)].Srivastava A., Santagostino E., Dougall A., Kitchen S., Sutherland M., Pipe S.W. et al. WFH guidelines for the management of hemophilia, 3rd ed. Haemophilia 2020;26 Suppl 6: 1–158.Gualtierotti R., Solimeno L.P., Peyvandi F. Hemophilic arthropathy: current knowledge and future perspectives. J Thromb Haemost 2021;19:2112–21.von Drygalski A., Chowdary P., Kulkarni R., Susen S., Konkle B.A., Oldenburg J. et al. Efanesoctocog alfa prophylaxis for patients with severe hemophilia A. N Engl J Med 2023;388:310–8.Malec L., Peyvandi F., Chan A.K.C., Königs C., Zulfikar B., Yuan H., Simpson M. et al. Efanesoctocog alfa prophylaxis for children with severe hemophilia A. N Engl J Med 2024;391:235–46.Warren B.B., Thornhill D., Stein J., Fadell M., Ingram J.D., Funk S. et al. Young adult outcomes of childhood prophylaxis for severe hemophilia A: results of the Joint Outcome Continuation Study. Blood Adv 2020;4:2451–9.Olivieri M., Kurnik K., Pfluger T., Bidlingmaier C. Identification and long-term observation of early joint damage by magnetic resonance imaging in clinically asymptomatic joints in patients with haemophilia A or B despite prophylaxis. Haemophilia 2012;18: 369–74.Жарков П.А. Современные возможности заместительной терапии и профилактики гемофилии А у детей. Педиатрия. Журнал им. Г.Н. Сперанского 2021; 100(2):182–7. [Zharkov P.A. Modern possibilities of substitution therapy and hemophilia A prevention in children. Pediatrics. Journal n. a. G.N. Speransky 2021;100(2):182–7. (In Russ.)].Raso S., Hermans C. Lonoctocog alfa (rVIII-SingleChain) for the treatment of haemophilia A. Expert Opin Biol Ther 2018;18(1):87–94.Chowdary P., Mullins E., Konkle B.A., McGuinn C., Shil Park Y., Stasyshyn O. et al. Long-term safety and efficacy results from the phase 3b, open-label, multicentre Continuation study of rurioctocog alfa pegol for prophylaxis in previously treated patients with severe haemophilia A. Haemophilia 2020;26(4): e168–78.Mahlangu J., Powell J.S., Ragni M.V., Chowdary P., Josephson N.C., Pabinger I. et al. Phase 3 study of recombinant factor VIII Fc fusion protein in severe hemophilia A. Blood 2014;123:317–25.Klukowska A., Sidonio R.F., Young G., Mancuso M.E., Álvarez-Román M.T., Bhatnagar N. et al. Simoctocog alfa (Nuwiq®) in children: early steps in life’s journey for people with severe hemophilia A. Ther Adv Hematol 2024;15:20406207241245511.Сырых Е.А., Алыева С.Н., Кучер О.А. Распространенность гемофильных артропатий у детей с гемофилией Воронежской области в зависимости от различных факторов. Молодежный инновационный вестник 2022;11(1):358–62. [Syrykh E.A., Alyeva S.N., Kucher O.A. The prevalence of hemophilic arthropathy in children with hemophilia in the Voronezh Region depending on different factors. Youth Innovation Bulletin 2022;11(1):358–62. (In Russ.)].Wilkins R.A., Stephensen D., Siddle H., Scott M.J., Xiang H., Horn E. et al. Twelve-month prevalence of haemarthrosis and joint disease using the Haemophilia Joint Health score: evaluation of the UK National Haemophilia Database and Haemtrack patient reported data: an observational study. BMJ Open 2022;12(1):e052358. DOI: 10.1136/bmjopen-2021-052358Kraft J., Blanchette V., Babyn P., et al. Magnetic resonance imaging and joint outcomes in boys with severe hemophilia A treated with tailored primary prophylaxis in Canada. J Thromb Haemost 2012;10(12):2494–502. DOI: 10.1111/jth.12025Roosendaal G., TeKoppele J.M., Vianen M.E., van den Berg H.M., Lafeber F.P., Bijlsma J.W. Blood-induced joint damage: a canine in vivo study. Arthritis Rheum 1999;42(5):1033–9.Jansen N.W., Roosendaal G., Wenting M.J., Bijlsma J.W.J., Theobald M., Hazewinkel H.A.W, Lafeber F.P.J.G. Very rapid clearance after a joint bleed in the canine knee cannot prevent adverse effects on cartilage and synovial tissue. Osteoarthritis Cartilage 2009;17(4): 433–40.Muniz R.L., Camelo R.M., Araújo M.S., Barbosa M.M., Afonso Guerra A., de Assis Acurcio F., Alvares-Teodoro J. Efficacy/effectiveness and safety of emicizumab prophylaxis of people with hemophilia A: a systematic review and meta-analysis. Expert Rev Hematol. 2023;16(12):1087–97. DOI: 10.1080/17474086.2023.2293096Callaghan M.U., Negrier C., PazPriel I., Chang T., Chebon S., Lehle M. et al. Long-term outcomes with emicizumab prophylaxis for hemophilia A with or without FVIII inhibitors from the HAVEN 1–4 studies. Blood 2021;137(16): 2231–42. DOI: 10.1182/blood. 2020009217Young G., Liesner R., Chang T., Sidonio R., Oldenburg J., Jiménez-Yuste V. et al. A multicenter, open-label phase 3 study of emicizumab prophylaxis in children with hemophilia A with inhibitors. Blood 2019;134(24):2127–38. DOI: 10.1182/ blood. 2019001869Жарков П.А., Воронин К.А., Андреева Т.А., Асекретова Т.В., Белкина Ю.Е., Демихов В.Г. и др. Значительное снижение количества кровотечений у детей с ингибиторной формой гемофилии А в реальной клинической практике применения эмицизумаба. Вопросы гематологии/онкологии и иммунопатологии в педиатрии 2022;21(1):66–71. DOI: 10.24287/1726-1708-2022-21-1-66-71 [Zharkov P.А., Voronin K.A., Andreeva T.A., Asekretova T.V., Belkina Yu.E., Demikhov V.G. et al. Bleeding rate reduction in children with hemophilia A and inhibitors treated with emicizumab in the real-world clinical setting. Pediatric Hematology/Oncology and Immunopathology 2022;21(1):66–71. (In Russ.)].Жарков П.А., Воронин К.А., Флоринский Д.Б., Андреева Т.А., Батдыева Д.Б., Горошкова М.Ю. и др. Применение эмицизумаба у детей с гемофилией А без ингибиторов в реальной клинической практике. Вопросы гематологии/онкологии и иммунопатологии в педиатрии 2023;22(4):96–101. DOI: 10.24287/1726-1708-2023-22-4-96101 [Zharkov P.A., Voronin K.A., Florinskiy D.B., Andreeva T.A., Batdiyeva D.B., Goroshkova M.Yu. et al. The use of emicizumab in children with hemophilia A without inhibitors in the real-world clinical setting. Pediatric Hematology/Oncology and Immunopathology 2023;22(4):96–101. (In Russ.)].Garcia J., Hammer M.R., Zia A. Serious bleeds in pediatric persons with hemophilia A on emicizumab prophylaxis. Res Pract Thromb Haemost 2023;7(8):102238. DOI: 10.1016/j.rpth.2023.102238Sherief L.M., Elagamy O., Darwish A., Soliman N.K., Elgendy M.R., Nazim A., Sobhi A. Emicizumab prophylaxis beyond clinical trials: a multicenter, prospective real-world study of pediatric hemophilia patients with and without inhibitors. Eur J Pediatr 2026;185(5):255. DOI: 10.1007/s00431-026-06872-zIorio A., Iserman E., Blanchette V., Dolan G., Escuriola Ettingshausen C., Hermans C. et al. Target plasma factor levels for personalized treatment in haemophilia: a Delphi consensus statement. Haemophilia 2017;23(3):e170–9.Khawaji M., Astermark J., Berntorp E. Lifelong prophylaxis in a large cohort of adult patients with severe haemophilia: a beneficial effect on orthopaedic outcome and quality of life. Eur J Haematol 2012;88: 329–35.Резолюция Совета экспертов, посвященного актуальным вопросам терапии пациентов с гемофилией А фактором свертывания крови VIII с пролонгированным периодом полувыведения (МНН – эфмороктоког альфа). Российский журнал детской гематологии и онкологии 2020;7(3):102–3. [Resolution of the Expert сouncil on сurrent issues in the treatment of patients with hemophilia A with clotting factor VIII with prolonged half-life (INN – Efmoroctocog alfa). Russian Journal of Pediatric Hematology and Oncology 2020;7(3):102–3. (In Russ.)].Андреева Т.А., Петров В.Ю., Константинова В.Н., Лавриченко И.А., Крашенинникова О.А., Залепухина О.Э., Позднякова В.А. Опыт применения эфмороктокога альфа у детей и подростков: клинические наблюдения. Педиатрия. Журнал им. Г.Н. Сперанского 2022;101(5):144–9. [Andreeva T.A., Petrov V.Yu., Konstantinova V.N., Lavrichenko I.A., Krasheninnikova O.A., Zalepuhina O.E., Pozdnyakova V.A. Use of efmoroctocog alfa in children and adolescents: clinical observations. Pediatrics. Journal n. a. G.N. Speransky 2022;101(5):144–9. (In Russ.)].Seth Chhabra E., Liu T., Kulman J., Patarroyo-White S., Yang B., Lu Q. et al. BIVV001, a new class of factor VIII replacement for hemophilia A that is independent of von Willebrand factor in primates and mice. Blood 2020;135: 1484–96.Fuller J.R., Knockenhauer K.E., Leksa N.C., Peters R.T., Batchelor J.D. Molecular determinants of the factor VIII/von Willebrand factor complex revealed by BIVV001 cryo-electron microscopy. Blood 2021;137:2970–80.Lissitchkov T., Willemze A., Jan C., Zilberstein M., Katragadda S. Pharmacokinetics of recombinant factor VIII in adults with severe hemophilia A: fixed-sequence single-dose study of octocog alfa, rurioctocog alfa pegol, and efanesoctocog alfa. Res Pract Thromb Haemost 2023;7:100176.Lissitchkov T., Willemze A., Katragadda S., Rice K., Poloskey S., Benson C. Efanesoctocog alfa for hemophilia A: results from a phase 1 repeat-dose study. Blood Adv 2022;6: 1089–94.Malec L., Peyvandi F., Chan A., Koenigs C., Zulfikar B., Yuan H. et al. Efanesoctocog alfa prophylaxis for previously treated patients <12 years of age with severe hemophilia A (LB 01.1). Res Pract Thromb Haemost 2023;7 (Suppl 2):1.Malec L., Nolan B., Chan A.K.C., Albisetti M., Chou S.-C., Zulfikar B. et.al. Plain language summary of two-year results of weekly efanesoctocog alfa treatment in children with severe haemophilia A: interim analysis of the XTEND-ed phase 3 study. Presented at the WFH Comprehensive Care Summit, April 23–25, 2025, Dubai, U.A.E. PP-045. [Electronic resource] URL: https://sciencelibrary.sobi.com/sites/default/files/ documents/Malec_XTEND-ed_kids_ PLS_WFHCCS2025_Poster.pdf. (accessed – 19.05.2026).Oldenburg J., Carcao M., Meunier S., Suzuki N., Alvarez Roman M.T., Neill G. et al. Treatment of bleeding episodes with efanesoctocog alfa in adults, adolescents, and children with severe haemophilia A: third interim analysis of the XTEND-ed long-term extension study. Presented at the 19th Annual Congress of the European Association for Haemophilia and Allied Disorders; 3–6 February 2026; Dublin, Ireland. P0069. [Electronic resource] URL: https://sciencelibrary.sobi.com/treatment-bleedingepisodes-efanesoctocog-alfa-adultsadolescents-and-children-severehaemophilia#a315. (accessed – 19.05.2026).Staber J., Weyand A., Khan U., Dumont J., Mamikonian L., Matino D. Clinical outcomes over 3 years of once-weekly efanesoctocog alfa treatment in adults and adolescents from north america with severe hemophilia A in the phase 3 XTEND-ed long-term extension study. Presented at Hemostasis & Thrombosis Research Society (HTRS). 2025 Scientific Symposium, Coronado, California, March 13–15, 2025. [Electronic resource] URL: https://sciencelibrary.sobi.com/ sites/default/files/documents/ Staber_XTEND-ed_NA_adults_ HTRS2025_Poster.pdf. (accessed – 19.05.2026).Janbain M., Escobar M.A., Carcao M., Wilson A., Dumont J., Ball N. et al. Real-world experience of switching to prophylactic efanesoctocog alfa in patients with moderate and severe hemophilia А: an analysis of the Adelphi Hemophilia Wave III Disease Specific Programme. Blood 2024;144 (Suppl 1):131.Klamroth R., Kragh N., Arnaud A., Guyot P., Wilson A., Wojciechowski P. et al. Efanesoctocog alfa versus standard and extended half-life factor VIII prophylaxis in adolescents and adults with severe hemophilia A. Adv Ther 2024;41:1–19.Álvarez Román M.T., Kragh N., Guyot P., Wilson A., Wojciechowski P., Margas W. et al. Efanesoctocog alfa versus emicizumab in adolescent and adult patients with haemophilia A without inhibitors. Adv Ther 2025;42(1):442–55.Klamroth R., Windyga J., Radulescu V., Collins P.W., Stasyshyn O., Mohd Ibrahim H. et al. Rurioctocog alfa pegol PK-guided prophylaxis in hemophilia A: results from the phase 3 PROPEL study. Blood 2021;137:1818–27.Oldenburg J., Mahlangu J.N., Kim B., Schmitt C., Callaghan M.U., Young G. et al. Emicizumab prophylaxis in hemophilia A with inhibitors. N Engl J Med 2017;377:809–18.Gringeri A., Lundin B., von Mackensen S., Mantovani L., Mannucci P.M.; ESPRIT Study Group. A randomized clinical trial of prophylaxis in children with hemophilia A (the ESPRIT Study). J Thromb Haemost 2011;9(4):700–10.Andersson N.G., Auerswald G., Barnes C., Carcao M., Dunn A.L., Fijnvandraat K. et al. Intracranial haemorrhage in children and adolescents with severe haemophilia A or B – the impact of prophylactic treatment. Br J Haematol 2017;179:298–307.